Chalcones, e.g., for use against parasitic infections are known from earlier patent applications assigned to the applicant, e.g. WO 93/17671, and WO 99/00114. Moderate antibacterial activity has been reported for a limited number of chalcones in earlier publications e.g. Haraguchi, H. et al Phytochemistry 1998, 48, 125-129 and Hatano, T. et al Chem. Pharm. Bull (Tokyo) 2000, 48, 1286-92.
The bioavailability of the known, neutral chalcones is low/not detectable due to the low solubility of the compounds. The compounds do not typically dissolve in the intestine and are therefore not available for absorption.
The spread of antimicrobial resistance determinants particular among nosocomial bacterial pathogens is an increasing problem. Such resistant pathogens include Staphylococcus aureus resistant to methicillin and thus to all β-lactam-antibiotics and Enterococci resistant to vancomycin (VRE). Such resistant bacteria pose a significant therapeutic challenge and bacterial strains resistant to all currently available antimicrobials are emerging. Furthermore, bacterial species intrinsically resistant to commonly employed antimicrobials are being recognized as important opportunistic pathogens in the setting of long-term immunocompromized patients. An example of this is Stenotrophomonas maltophilia which possesses a β-lactamase rendering the bacteria intrinsically resistant to carbapenems. As cross-resistance within a given class of antibiotics often occurs the development of new classes of antibiotics is a necessity to counter the emerging threat of bacterial resistance.
The resistance of Plasmodium falciparum to chloroquine and other antimalarial drugs have created an urgent need for new drugs that are safe and effective for the prophylaxis and treatment of malaria.
Furthermore, the increasing appearance of resistance to first line antileishmanial drugs, e.g. Pentostam or Glucantime, emphasizes the need for new drugs for the treatment of Leishmania infections.
Thus, there is a need for chalcone derivatives with improved therapeutic or prophylactic activity against parasites and bacteria.